It is estimated that 36 million Americans suffer from seasonal allergies and that ragweed is the primary cause of autumn allergies, 87% of patients with ragweed allergy suffer rhinoconjunctivitis. ToleroMune Ragweed is a novel, synthetic, allergen-derived peptide desensitising vaccine, currently being developed for the treatment of ragweed allergy.

The purpose of the present study is to evaluate the safety and tolerability of multiple ascending doses of ToleroMune Ragweed in subjects in subjects with a documented history of allergic rhinoconjunctivitis on exposure to ragweed pollen. The efficacy of ToleroMune Ragweed will also be explored in these subjects using the Late Phase Skin Response, Early Phase Skin Response and Conjunctival Provocation Test.

Mean change from baseline in area of the LPSR 8 hours after intradermal challenge with whole ragweed allergen at PTC after ToleroMune Ragweed injection compared to placebo [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]

Mean change from baseline in area of the EPSR 15 minutes after intradermal challenge with whole ragweed allergen at PTC after ToleroMune Ragweed injection compared to placebo [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]

ToleroMune Ragweed, subjects to receive either active or placebo comparator

Biological: ToleroMune Ragweed

ToleroMune Ragweed dose 1x4 administrations 2 weeks apart

Biological: Placebo

Placebo comparator, 1x4 administrations 2 weeks apart

Experimental: Cohort 2

ToleroMune Ragweed or placebo comparator

Biological: ToleroMune Ragweed

ToleroMune Ragweed dose 1x4 administrations 2 weeks apart

Biological: Placebo

Placebo comparator, 1x4 administrations 2 weeks apart

Experimental: Cohort 3

ToleroMune Ragweed or placebo comparator

Biological: ToleroMune Ragweed

ToleroMune Ragweed dose 1x4 administrations 2 weeks apart

Biological: Placebo

Placebo comparator, 1x4 administrations 2 weeks apart

Experimental: Cohort 4

ToleroMune Ragweed or placebo comparator

Biological: ToleroMune Ragweed

ToleroMune Ragweed dose 1x4 administrations 2 weeks apart

Biological: Placebo

Placebo comparator, 1x4 administrations 2 weeks apart

Experimental: Cohort 5

ToleroMune Ragweed or placebo comparator

Biological: ToleroMune Ragweed

ToleroMune Ragweed dose 1x4 administrations 2 weeks apart

Biological: Placebo

Placebo comparator, 1x4 administrations 2 weeks apart

Detailed Description:

This study is designed as a randomised, double-blind, placebo-controlled study to evaluate the safety and tolerability of escalating multiple doses of ToleroMune Ragweed in subjects with a documented history of allergic rhinoconjunctivitis on exposure to ragweed pollen. The efficacy of ToleroMune Ragweed will also be explored in these subjects using the LPSR, EPSR, CPT and levels of ragweed specific IgE. A single centre will be initiated first, with a second centre included as a backup, if needed, to enable recruitment numbers to be met.

The study will consist of 3 study periods. In Period 1, Screening will be performed up to a maximum of 8 weeks before randomisation and may consist of one or two visits to the clinic, at the Investigator's discretion. Baseline Challenge will consist of a single visit 1 to 4 weeks before randomisation.

Period 2 (Treatment Period) will consist of 4 visits (Visits 3A-3D) two weeks apart (14±2 days). Subjects who comply with the inclusion/exclusion criteria will be assigned to one of 5 dose groups. The first dose group will receive 4 administrations of ToleroMune Ragweed. Successive dose groups will increasing doses given as 4 administrations of ToleroMune Ragweed, provided the first administration of the previous dose was safe and well tolerated.

In Period 3, Post-treatment Challenge will take place 19-25 weeks after the first administration in the Treatment Period and will be timed to be outside the Ragweed season. However in the event that the Ragweed season lasts beyond 26th October 2009, the PTC will take place 22-28 weeks after the first administration in the Treatment Period. Assessments performed will be identical to those at the Baseline Challenge. Follow-up will be conducted 3-10 days after PTC.

Eligibility

Ages Eligible for Study:

18 Years to 65 Years (Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Male or female, aged 18-65 years

A reliable, documented history of rhinoconjunctivitis (sneezing, rhinorrhoea, nasal blockage, itchy/red/sore/watering eyes) on exposure to ragweed for at least 2 years

Allergy to ragweed, defined by positive skin prick test at the Screening Visit

Subjects who are normally active and otherwise judged to be in good health

The subject must be willing and able to comply with the study requirements

If the subject is female and of childbearing potential she must practice an acceptable form of contraception, and produce a negative urine pregnancy test on the Screening Visit. A female subject may be included without a negative urine pregnancy test if she can document that she is surgically sterile or at least 2 years post-menopausal

Exclusion Criteria:

Subjects with an FEV1 <80% of normal

Subjects who suffer from other seasonal allergies, and cannot complete the clinical study outside the pollen season or are symptomatic for significant perennial rhinitis

A history of anaphylaxis to ragweed allergen; subjects who have a history of severe drug allergy, angioedema or anaphylactic reactions to food

Subjects with a history of asthma

Subjects who have auto-immune or rheumatoid diseases

Clinical history of immunodeficiency, including immunosuppressant therapy

Subjects in whom tyrosine metabolism is disturbed

Current diagnosis of chickenpox or measles or exposure in the last 3 weeks

Active or quiescent tuberculous infection of the respiratory tract, untreated local or systemic fungal or bacterial or systemic viral infections or parasitic or ocular herpes simplex

Have symptoms of a clinically relevant illness, in the Investigator's opinion, within 6 weeks prior to Screening Visit

Allergen immunotherapy during the last 5 years or ragweed immunotherapy ever.

Subjects who have completed or are undergoing ongoing treatment with anti-IgE-antibody

Use of the therapies listed in Section 5.9.2 at any time during the study will make the subject ineligible for the study

The subject has unacceptable symptoms in the 3 days without loratadine prior to the screening visit

Female subjects who are pregnant, lactating or planning a pregnancy during the study

Have any clinically relevant abnormalities detected on physical examination

12-lead ECG or vital signs (blood pressure, pulse rate, respiratory rate and oral temperature) that are outside normal limits, unless the abnormality is considered not to be of clinical relevance by the Investigator

Laboratory values (haematology, biochemistry, urine tests) that are outside the normal ranges, unless the abnormality is considered not to be of clinical relevance by the Investigator

Significant history of alcohol or drug abuse

History of immunopathological disease

Positive test for hepatitis B, hepatitis C or HIV at screening

Have previously been randomised into this study

Planned travel outside the study area for a substantial portion of the study period

Have received treatment with an investigational drug within 6 months prior to study screening or have participated in a study with a new formulation of a marketed drug one month prior to study screening

Have any significant disease or disorder (e.g. cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the study, or the subject's ability to participate in the study

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00878774